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Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection

Conditions
Heart Transplant Rejection
Registration Number
NCT04973943
Lead Sponsor
Puerta de Hierro University Hospital
Brief Summary

FreeDNA-CAR is a prospective, observational multicenter study, that will include a total of 200 adult heart transplant (HT) patients from 14 centers in Spain. Our main objective is to test donor-derived Cell-Free DNA (dd-cfDNA) against endomyocardial biopsy (EMB) for the diagnosis of acute cellular rejection.

Detailed Description

All patients will be enrolled immediately after HT, and will undergo undergo routine surveillance EMB at 15 days, 1 month, 2, 3, 4, 6 and 12 months after HT. Simultaneously with each EMB, dd-cfDNA will be measured in plasma.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
200
Inclusion Criteria
  • Patients > 18 years old who undergo heart transplant during the recruiting period
Exclusion Criteria
  • Patients with moderate or severe Primary Graft Dysfunction
  • Patients on invasive mechanical ventilation 15 days after heart transplant
  • Patients on renal replacement therapy, continuous or periodic, 15 days after heart transplant
  • Heart Transplant due to a cardiomyopathy that could potentially recur on the graft (cardiac amyloidosis, Chagas disease or sarcoidosis, amongst others)
  • Multiorgan transplant

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Association between dd-cfDNA levels and the presence of acute cellular rejection1 year

Association between dd-cfDNA levels above a certain cut-point and the presence of treatable acute cellular rejection as determined by endomyocardial biopsy (graded by International Society of Heart and Lung Transplantation 2010 classification, grade \> 1R).

Secondary Outcome Measures
NameTimeMethod
Area under curve for dd-cfDNA1 year

To define a cutt-off point of dd-cfDNA level with a high negative predictive value that could obviate the need to perform surveillance endomyocardial biopsies

Correlation between dd-cfDNA and antibody mediated rejection (AMR)1 year

Correlation between dd-cfDNA and antibody mediated rejection (AMR)

Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR)1 year

Determine a cut-off point of dd-cfDNA that allows to differentiate between acute cellular rejection (ACR) and antibody mediated rejection (AMR)

Association between dd-cfDNA and immunosuppressive (IS) treatment1 year

Subanalysis of association between dd-cfDNA and rejection stratified by IS regimen (type and dose of drug).

Association between dd-cfDNA (%) and left ventricular ejection fraction1 year

Association between dd-cfDNA and left ventricular ejection fraction (LVEF). All echocardiograms will be performed on the same day of EMB.

Determine the biomarker's kinetics at 15 days post-transplant15 days

Determine dd-cfDNA levels at 15 days post-transplant in absence of rejection

Association between dd-cfDNA levels and cytomegalovirus (CMV) infection1 year

Association between dd-cfDNA levels and CMV infection as determined by CMV polymerase chain reaction (number of copies per ml)

Trial Locations

Locations (12)

Clinica Universitaria de Navarra

🇪🇸

Pamplona, Navarra, Spain

Hospital Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

University Hospital Puerta de Hierro

🇪🇸

Majadahonda, Madrid, Spain

Hospital Universitario A Coruña

🇪🇸

A Coruña, Spain

Hospital 12 octubre

🇪🇸

Madrid, Spain

Hospital Bellvitge

🇪🇸

Barcelona, Spain

Hospital La Fe

🇪🇸

Valencia, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Virgen de la Arrixaca

🇪🇸

Murcia, Spain

Hospital Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

Hospital Universitario Central de Asturias

🇪🇸

Oviedo, Asturias, Spain

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